OPIATE-MEDIATED INHIBITION OF CALCIUM SIGNALING IS DECREASED IN DORSAL-ROOT GANGLION NEURONS FROM THE DIABETIC BB W RAT/

The effect of diabetes mellitus on opiate-mediated inhibition of calci um current density (I-DCa [pA pF(-1)]) and cytosolic calcium response ([Ca2+](i) nM) to depolarization with elevated KCl and capsaicin was a ssessed, Experiments were performed on isolated, acutely dissociated d orsal root ganglion (DRG) neurons from diabetic. BioBreeding/Worcester (BB/W) rats and age-matched control animals, Sciatic nerve conduction velocity was significantly decreased in diabetic animals compared to controls, Mean I-DCa and [Ca2+](i) responses to capsaicin and elevated KCl recorded in DRGs from diabetic animals were significantly larger than those recorded in DRG neurons from controls. In neurons from diab etic animals, the opiate agonist dynorphin A (Dyn A; 1, 3, and 5 mu M) had significantly less inhibitory effect on I-DCa and KCl-induced [Ca 2+](i) responses compared to controls, Omega-conotoxin GVIA (omega-CgT X; 10 mu M) and pertussis toxin (PTX; 250 ng ml(-1)) abolished Dyn A-m ediated inhibition of I-DCa and [Ca2+](i) in control and diabetic neur ons, suggesting that Dyn A modulated predominantly N-type calcium chan nels coupled to opiate receptors via PTX-sensitive (G(i/o)) inhibitory G proteins, These results suggest that opiate-mediated regulation of PTX-sensitive, G protein-coupled calcium channels is diminished in dia betes and that this correlates with impaired regulation of cytosolic c alcium.